Objective To elucidate the impact of CD146 on epithelial-mesenchymal transition (EMT) of acquired resistance to erlotinib in non-small cell lung cancer (NSCLC),thus to reveal the molecular mechanism of CD146 involved in the EMT and in the metastasis of cancer cells.Methods NSCLC cell line H1650 was used to establish the subline resistant to erlotinib (H1650ER).The expression of E-cadherin,Vimentin and CD146 in the resistant cells was examined using immunostaining and Western blotting.CD146 was silenced by RNA interference in H1650ER,and invasion assay was performed to characterize the resistant cells.The effects of CD146 on cell proliferation and invasion were analyzed.Results The quantity of CD146 expression and Vimentin expression in lung adenocarcinoma cancer cell H1650ER were 0.474 ± 0.013 and 0.465 ± 0.012,significantly higher than before resistance (P ＜ 0.05).The E-cadherin protein expression was 0.180 ± 0.011,significantly lower than before resistance (P ＜ 0.05).As compared with the control group,small interfering RNA (siRNA)-mediated down-regulation of CD146 suppressed the proliferation and invasion ability of H1650ER (P ＜ 0.05).Conclnsion CD146 contributes to EMT of acquired resistance to erlotinib in NSCLC in vitro.It suggests that CD146 is a potential molecular target in the treatment of NSCLC.